The role of DNA methylation in cancer pathogenesis has been investigated to a great extent in multiple cancer types. In particular, the methylation of CpG islands (CGIs) in the 5′ promoter gene region has been known to suppress the transcription of tumor suppressor genes leading to tumorigeneisis. The retinoblastoma family gene p14INK4a is a well-known example [1]. More specifically, methylation of the CGIs in the gene promoter region has been shown to silence RNA expression leading to upstream effects that can change the activation status of several cancer related pathways [2]. Because of the extended effect methylation can have on cancer, it has been successfully used as a biomarker of treatment response and prognosis in some cancer types. For example, MGMT methylation has been identified as a biomarker of positive response to temozolamide and radiation in patients with glioblastoma [3]. Recent work in gliomas has identified a set of patients that exhibit hypermethylation in multiple loci, termed Glioma CpG Island Hypermethylator Phenotype (G-CIMP) [4, 5]. These patients have been found to harbor IDH1 mutations that cause the hypermethylator phenotype, a well-known genetic abnormality in gliomas [6]. However, most studies attempting to identify methylation markers of tumor prognosis have been limiting their interest in methylation signatures identified within CGI in the 5′ promoter region of known genes. This is mainly because the biological relation between methylation and transcription is best understood in the 5′ gene region while their true biological relation in other genomic regions such as the gene body is not well studied and thus so far unappreciated.